Affinage

GULP1

PTB domain-containing engulfment adapter protein 1 · UniProt Q9UBP9

Length
304 aa
Mass
34.5 kDa
Annotated
2026-06-10
44 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GULP1 (the mammalian ortholog of C. elegans CED-6) is a PTB-domain adaptor protein that acts within engulfing cells to transduce 'eat-me' signals required for the phagocytosis of apoptotic cells, a function conserved from worms to humans (PMID:9635426, PMID:10574771, PMID:10574763). It dimerizes through a leucine zipper immediately adjacent to its PTB domain, and uses that PTB domain to dock onto NPXY-type motifs in the cytoplasmic tails of a broad set of engulfment receptors including CED-1, CD91/LRP1, stabilin-1, stabilin-2, SR-BI, and Jedi-1 (PMID:10734103, PMID:11729193, PMID:18230608, PMID:19122200, PMID:20599701, PMID:24743597). Downstream of receptor engagement GULP1 nucleates the cytoskeletal and membrane machinery for engulfment: it couples to clathrin to assemble phosphoclathrin-coated phagocytic structures (PMID:17007823, PMID:22398720, PMID:24743597), positively regulates Arf6 by sequestering the Arf6-GAP ACAP1 (PMID:17398097), and activates p38/ERK–Rac1 signaling to drive actin remodeling (PMID:19122200); in EphB/ephrin trogocytosis it cooperates with the Rac-GEF Tiam2 and is required to recruit dynamin for membrane scission (PMID:31409653). Through its association with LRP1, GULP1 also governs endosomal ligand trafficking and lipid homeostasis and tunes the duration of TGF-β/SMAD signaling (PMID:16497666, PMID:22451657, PMID:38553249). Beyond engulfment, GULP1 binds the NPTY motif of APP to promote amyloidogenic processing (PMID:21486224), interacts with KEAP1 to retain NRF2 in the cytoplasm with consequences for cisplatin sensitivity in urothelial/bladder cancer (PMID:32817372, PMID:34576193, PMID:39467629), and binds ATG14 to target it to the ER and potentiate PI3KC3-C1–driven autophagy (PMID:39080084). In vivo, GULP1 loss in mice perturbs osteoclast, tendon, and cardiac biology, and it engages IKIP to modulate NF-κB/OPA1-dependent mitochondrial maintenance (PMID:36870066, PMID:40747745, PMID:42015218).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1998 High

    Established that CED-6 is an adaptor acting inside the engulfing cell rather than the dying cell, defining the genetic logic of apoptotic corpse clearance.

    Evidence Genetic cloning and mosaic loss-of-function analysis in C. elegans

    PMID:9635426

    Open questions at the time
    • No biochemical receptor partner identified at this stage
    • Mammalian relevance not yet demonstrated
  2. 1999 Medium

    Showed the engulfment role is evolutionarily conserved, validating human GULP1 as the functional ortholog acting in macrophage phagocytosis of apoptotic cells.

    Evidence Heterologous rescue of ced-6 mutants and overexpression phagocytosis assay in primary human macrophages

    PMID:10574763 PMID:10574771

    Open questions at the time
    • Single-lab functional assays
    • Direct receptor interaction not yet mapped
  3. 2000 High

    Defined the structural basis for GULP1 oligomerization, showing a conserved leucine zipper adjacent to the PTB domain mediates dimerization.

    Evidence Co-IP, yeast two-hybrid, gel filtration, and mutagenesis across species

    PMID:10734103

    Open questions at the time
    • Functional consequence of dimerization for receptor binding not resolved
  4. 2001 High

    Identified the receptor-recognition mechanism: the PTB domain binds NPXY motifs in CED-1 and human CD91/LRP cytoplasmic tails, linking the adaptor to engulfment receptors.

    Evidence Co-IP, yeast two-hybrid, pull-down, and domain mapping mutagenesis

    PMID:11729193

    Open questions at the time
    • Did not test the full repertoire of receptors GULP1 engages
    • Downstream effectors of the receptor complex unknown
  5. 2006 High

    Extended GULP1 function beyond canonical phagocytosis, implicating it in glial axon-pruning engulfment, neuronal/synaptic localization, clathrin binding, and LRP-dependent lipid trafficking.

    Evidence Drosophila glia-specific RNAi and genetic interaction; rat fractionation, yeast two-hybrid/GST pull-down; bidirectional gain/loss-of-function lipid trafficking assays

    PMID:16497666 PMID:16772168 PMID:17007823

    Open questions at the time
    • Mechanistic link between clathrin binding and engulfment not yet established
    • How GULP1 controls LRP ligand sorting mechanistically unclear
  6. 2007 High

    Placed GULP1 in small-GTPase signaling, showing it positively regulates Arf6 by sequestering the GAP ACAP1, connecting the adaptor to membrane trafficking and migration.

    Evidence Direct binding assays, tripartite complex Co-IP, Arf6-GTP measurement, and migration assays

    PMID:17398097

    Open questions at the time
    • Link between Arf6 regulation and engulfment not directly tested
    • No structural model of the GULP1/ACAP1/Arf6 complex
  7. 2008 High

    Generalized the NPXY-PTB receptor paradigm to stabilin-2, demonstrating GULP1 is rate-limiting for stabilin-2-mediated clearance of aged red blood cells.

    Evidence FRET, Co-IP, domain mutagenesis, dominant-negative PTB, and bidirectional phagocytosis assays

    PMID:18230608

    Open questions at the time
    • Downstream cytoskeletal machinery for stabilin-2 engulfment not defined here
  8. 2009 High

    Resolved a signaling cascade downstream of receptor binding: GULP1 with SR-BI activates p38/ERK to elevate Rac1-GTP and drive actin rearrangement for phagocytosis.

    Evidence Yeast two-hybrid, cell-free binding, Co-IP, MAPK-inhibitor epistasis, GTP-Rac1 measurement, and phagocytosis assays

    PMID:19122200

    Open questions at the time
    • How GULP1 mechanistically activates MAPK upstream is not defined
  9. 2010 Medium

    Added stabilin-1 to the receptor set, reinforcing the NPxF/Y-PTB recognition mode in phosphatidylserine-mediated engulfment.

    Evidence Co-IP, colocalization, siRNA knockdown, and phagocytosis assay

    PMID:20599701

    Open questions at the time
    • Single-lab characterization
    • Effector pathway downstream of stabilin-1 not detailed
  10. 2011 High

    Revealed a non-engulfment substrate, showing GULP1 binds the APP NPTY motif and promotes amyloidogenic CTF/Aβ generation.

    Evidence Yeast two-hybrid, Co-IP, reporter assay, and bidirectional expression with Aβ/CTF readouts

    PMID:21486224

    Open questions at the time
    • Trafficking step at which GULP1 alters APP processing not pinpointed here
  11. 2012 High

    Mechanistically unified GULP1 as a clathrin adaptor and an endosomal signaling modulator, recognizing noncanonical sorting sequences and prolonging LRP1-dependent TGF-β/SMAD3 signaling.

    Evidence Drosophila ced-6 null genetics, uptake assays in HeLa, clathrin-coated vesicle fractionation; SMAD3 phosphorylation, endosomal trafficking, and functional TGF-β assays

    PMID:22398720 PMID:22451657

    Open questions at the time
    • How GULP1 selects between cargo-internalization and signaling-endosome retention is unresolved
  12. 2013 Medium

    Identified a nuclear function, showing GULP1 shuttles and mediates LRP1- (but not APP-) intracellular-domain transactivation.

    Evidence Nuclear fractionation/trafficking and reporter-based transactivation assays

    PMID:23167255

    Open questions at the time
    • Target genes of LRP1-ICD/GULP1 transactivation not identified
    • Single-lab evidence
  13. 2014 High

    Connected receptor binding to membrane remodeling, showing GULP1 bridges Jedi-1 to clathrin heavy chain whose tyrosine phosphorylation drives phosphoclathrin/actin assembly at phagocytic cups.

    Evidence Co-IP, NPXY mutagenesis, reciprocal GULP/CHC knockdown, and phagocytosis assays with beads and apoptotic neurons

    PMID:24743597

    Open questions at the time
    • Kinase responsible for CHC phosphorylation not identified
  14. 2019 High

    Demonstrated GULP1 orchestrates trogocytosis, dynamically engaging EphB/ephrin clusters with Tiam2/Rac and serving as a prerequisite for dynamin recruitment and membrane scission, and that αvβ3 integrin transcriptionally suppresses GULP1.

    Evidence Live imaging, knockdown/knockout, Co-IP, Xenopus embryo assays; trabecular meshwork siRNA, phagocytosis, qPCR

    PMID:31409653 PMID:31516309

    Open questions at the time
    • Mechanism by which GULP1 recruits dynamin is not structurally defined
    • Integrin-to-GULP1 transcriptional pathway not mapped
  15. 2020 Medium

    Established a stress/redox role, showing GULP1 binds KEAP1 to retain NRF2 cytoplasmically, and its loss drives constitutive NRF2 target activation and cisplatin resistance.

    Evidence Co-IP, siRNA knockdown, NRF2 localization, gene expression, and tumor growth assays

    PMID:32817372

    Open questions at the time
    • Whether KEAP1 binding requires the PTB domain not addressed
    • Single-lab study
  16. 2024 High

    Defined an autophagy function: GULP1 binds ATG14 and targets it to the ER to potentiate PI3KC3-C1 activity, simultaneously promoting APP entry into autophagic vacuoles.

    Evidence Co-IP, PI3KC3-C1 activity assay, confocal ER-targeting, autophagy flux, mutagenesis, and APP CTF/Aβ measurement

    PMID:39080084

    Open questions at the time
    • Relationship between the autophagy role and the clathrin/engulfment role unclear
  17. 2024 Medium

    Showed GULP1 expression is hormonally controlled (AR and ERβ directly repress its promoter) with downstream consequences for chondrocyte differentiation via TGF-β/SMAD2/3 and for cisplatin sensitivity.

    Evidence ChIP, AR/ERβ over- and knockdown, siRNA GULP1 knockdown, drug cytotoxicity, cell cycle and chondrogenic differentiation assays

    PMID:34576193 PMID:38553249 PMID:39467629

    Open questions at the time
    • Mechanism linking GULP1 loss to cisplatin-specific resistance not fully resolved
    • Single-lab studies
  18. 2026 Medium

    Extended GULP1 to in vivo tissue physiology, with knockout phenotypes in bone (estrogen/osteoclast), tendon (ERK/collagen), and an IKIP/NF-κB/OPA1 axis governing mitochondrial morphology in diabetic cardiomyopathy.

    Evidence Gulp1 KO and cardiac-specific KO/knock-in mice, microCT, histomorphometry, GC-MS steroid measurement, BrdU/TEM, Co-IP, echocardiography, and metabolic assays

    PMID:36870066 PMID:40747745 PMID:42015218

    Open questions at the time
    • How the adaptor/engulfment activity relates to these tissue phenotypes is unclear
    • Single-lab models for each tissue

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how GULP1's many context-specific activities (receptor engulfment adaptor, clathrin/Arf6 trafficking regulator, KEAP1/NRF2 and autophagy modulator, and tissue developmental factor) are integrated or selectively deployed in different cell types.
  • No structural model integrating PTB, leucine zipper, and partner binding
  • No unifying regulatory logic for partner selection established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005768 endosome 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-8953897 Cellular responses to stimuli 1 R-HSA-9612973 Autophagy 1
Partners
ACAP1ATG14JEDI-1KEAP1LRP1SCARB1STAB1STAB2

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 CED-6 (GULP1 ortholog in C. elegans) was cloned and shown by genetic mosaic analysis to act within engulfing cells (not dying cells) as an adaptor protein with an N-terminal PTB domain, specifically required for the engulfment of apoptotic cells at both early and late stages of apoptosis. Genetic cloning, mosaic analysis, loss-of-function in C. elegans Cell High 9635426
1999 Human CED-6 (GULP1/hCED-6) rescues the engulfment defect of C. elegans ced-6 mutants, demonstrating functional conservation; the protein contains a PTB domain, predicted coiled-coil domain, and potential SH3-binding sites. Heterologous rescue in C. elegans, cDNA characterization Current biology : CB Medium 10574771
1999 Overexpression of human CED-6 (GULP1) in primary human macrophages promotes phagocytosis specifically of apoptotic cells but not non-apoptotic cells, confirming it as the mammalian orthologue involved in a conserved apoptotic engulfment pathway. Phagocytosis assay with lacZ-positive apoptotic cells in transgenic macrophages, overexpression Current biology : CB Medium 10574763
2000 CED-6/GULP1 dimerizes through a leucine zipper domain immediately adjacent to the PTB domain; this dimerization is conserved across C. elegans, rodent, and human CED-6 and is necessary and sufficient for dimer formation. Co-immunoprecipitation, yeast two-hybrid assays, gel filtration, mutational analysis The Journal of biological chemistry High 10734103
2001 GULP1/CED-6 physically interacts with the NPXY motif in the cytoplasmic tail of CED-1 (C. elegans engulfment receptor) and with a specific NPXY motif in the human CD91/LRP cytoplasmic tail; this interaction is mediated by the GULP PTB domain and was demonstrated by biochemical approaches and yeast two-hybrid analysis. Co-immunoprecipitation, yeast two-hybrid, biochemical pull-down, mutational analysis The Journal of biological chemistry High 11729193
2006 In Drosophila, draper and ced-6 function in glial cells (not in the axons being pruned) to mediate engulfment of degenerating larval axons during metamorphosis; glia-specific RNAi knockdown of ced-6 suppresses glial engulfment and inhibits axon pruning, and drpr and ced-6 interact genetically in this glial action. Drosophila genetics, glia-specific RNAi knockdown, genetic interaction analysis Neuron High 16772168
2006 GULP1 overexpression impairs trafficking of LRP ligands alpha2-macroglobulin and prosaposin, resulting in glycosphingolipid and free cholesterol accumulation in late endosomes/lysosomes and decreased ABCA1-mediated cholesterol efflux; conversely, GULP1 knockdown promotes prosaposin targeting to late endosomes and enhances cholesterol clearance, revealing a GULP/LRP/ABCA1 triad in lipid homeostasis. Overexpression and knockdown (siRNA), biochemical lipid assays, confocal microscopy, ligand trafficking assays The Journal of biological chemistry Medium 16497666
2006 Rat CED-6 (GULP1 orthologue) is expressed in neurons (not glia) and localizes to synaptosomes; the PTB-containing CED-6 interacts with clathrin as demonstrated by yeast two-hybrid and GST pull-down, and colocalizes with clathrin-coated vesicles in cultured cells. Subcellular fractionation, immunohistochemistry, yeast two-hybrid, GST pull-down, colocalization by fluorescence microscopy Brain research Medium 17007823
2007 GULP1 acts as a positive regulator of Arf6: its PTB domain directly binds GDP-bound Arf6, GULP associates with Arf6-GAP ACAP1, GULP reverses ACAP1-mediated Arf6-GTP decrease and counter-acts ACAP1 inhibition of cell migration, and GULP, ACAP1, and GDP-Arf6 form a tripartite complex suggesting sequestration of ACAP1 as a mechanism. Biochemical binding assays, Co-IP, Arf6-GTP measurement, cell migration assay, knockdown and overexpression Current biology : CB High 17398097
2008 GULP1 physically and functionally interacts with the cytoplasmic tail of stabilin-2 through its PTB domain binding the NPXY motif; GULP knockdown decreases and GULP overexpression increases stabilin-2-mediated phagocytosis of aged red blood cells; a TAT-PTB domain fusion acts as dominant negative to impair engulfment. FRET analysis, Co-immunoprecipitation, knockdown/overexpression, phagocytosis assay, dominant negative PTB domain The Journal of biological chemistry High 18230608
2009 SR-BI binds GULP1 via its C-terminal intracellular domain (yeast two-hybrid and cell-free binding assay), and GULP1 forms a complex with SR-BI in cells prior to PS activation; upon PS stimulation, GULP1 activates MAPK p38 and ERK1/2, which in turn elevates GTP-bound Rac1, driving actin cytoskeleton rearrangement for phagocytosis. Yeast two-hybrid, cell-free binding assay, co-immunoprecipitation, siRNA knockdown, GTP-Rac1 measurement, MAPK inhibitor experiments, phagocytosis assay Journal of biochemistry High 19122200
2010 GULP1 specifically interacts with the NPxF/Y motif of stabilin-1 cytoplasmic region via its PTB domain, co-localizes with stabilin-1 around PS-coated beads, and GULP knockdown decreases stabilin-1-mediated phagocytosis. Co-immunoprecipitation, colocalization by fluorescence microscopy, siRNA knockdown, phagocytosis assay Biochemical and biophysical research communications Medium 20599701
2011 GULP1 interacts with the NPTY motif of APP via its PTB domain (yeast two-hybrid and co-IP), co-localizes with APP in neurons, enhances APP C-terminal fragment and Aβ generation upon overexpression, and reduces CTF/Aβ production upon knockdown. Yeast two-hybrid, co-immunoprecipitation, confocal microscopy, APP-GAL4 reporter assay, overexpression and knockdown with Aβ/CTF measurement The Biochemical journal High 21486224
2012 Drosophila Ced-6 (GULP1 ortholog) operates as a clathrin adaptor in clathrin-mediated endocytosis: its PTB domain recognizes the noncanonical FXNPXA sorting sequence of the vitellogenin receptor Yolkless, and Ced-6 promotes clathrin-dependent uptake of Yolkless chimeras in HeLa cells; human GULP similarly binds clathrin machinery, localizes to cell-surface clathrin-coated structures, and is enriched in placental clathrin-coated vesicles. Genetic analysis (ced-6-null flies), biochemical binding assays, uptake assays in HeLa cells, fractionation of placental clathrin-coated vesicles Molecular biology of the cell High 22398720
2012 GULP1 regulates TGF-β signaling in ovarian cells through LRP1 (TGF-β receptor V): GULP overexpression retains TGF-β in signaling-competent early endosomes, prolongs SMAD3 phosphorylation, and enhances growth inhibition, migration, and invasion responses to TGF-β; GULP knockdown/absence shortens SMAD3 phosphorylation and impairs growth inhibition. SMAD3 phosphorylation assay (western blot), TGF-β growth inhibition assay, migration/invasion assay, endosomal trafficking analysis, overexpression and antisense knockdown The Journal of biological chemistry Medium 22451657
2013 GULP1 is a nucleocytoplasmic shuttling protein that mediates transactivation specifically with LRP1 (but not APP) intracellular domain, as demonstrated by differential nuclear trafficking and reporter-plasmid-based transactivation assay. Nuclear fractionation/trafficking assays, reporter-plasmid-based transactivation assay, co-expression with APP and LRP1 The Biochemical journal Medium 23167255
2014 GULP1 associates with Jedi-1 (an engulfment receptor) via the NPXY motif and promotes Jedi-1-mediated phagocytosis through binding to clathrin heavy chain (CHC); during engulfment CHC is tyrosine phosphorylated (required for engulfment), and both phosphoclathrin and actin accumulate around engulfed targets; CHC knockdown prevents Jedi-1-mediated engulfment of both microspheres and apoptotic neurons. Co-immunoprecipitation, NPXY motif mutagenesis, siRNA knockdown of GULP and CHC, phagocytosis assay with microspheres and apoptotic neurons, immunofluorescence Molecular biology of the cell High 24743597
2019 GULP1 regulates EphB/ephrinB trogocytosis bi-directionally by dynamically engaging with EphB/ephrinB protein clusters in cooperation with the Rac-GEF Tiam2, and its presence at the Eph/ephrin cluster is a prerequisite for recruiting the endocytic GTPase dynamin, enabling membrane scission and engulfment during cell rearrangements in cultured cells and embryonic development. Live imaging, knockdown/knockout, co-immunoprecipitation, fluorescence microscopy, Xenopus embryo cell rearrangement assays The Journal of cell biology High 31409653
2019 siRNA knockdown of GULP1 in human trabecular meshwork cells decreases phagocytosis by ~40%, and GULP1 mRNA levels are decreased ~60% by αvβ3 integrin overexpression, indicating that αvβ3 integrin negatively regulates GULP1 expression and thereby suppresses engulfment. siRNA knockdown, phagocytosis assay (pHrodo-labeled bioparticles), qPCR, western blot Molecular vision Medium 31516309
2020 GULP1 is a KEAP1-binding protein that maintains actin cytoskeleton architecture and helps KEAP1 sequester NRF2 in the cytoplasm; GULP1 silencing causes nuclear accumulation of NRF2, constitutive NRF2 target gene activation (HMOX1 and other antioxidant genes), and confers cisplatin resistance in urothelial carcinoma. Co-immunoprecipitation (GULP1-KEAP1 interaction), siRNA knockdown, NRF2 nuclear localization assay, in vitro and in vivo tumor growth assays, gene expression analysis Science signaling Medium 32817372
2021 Androgen receptor (AR) directly binds the promoter region of GULP1 (chromatin immunoprecipitation), and androgen treatment or AR overexpression reduces GULP1 expression; GULP1 knockdown in bladder cancer increases cisplatin resistance, decreases apoptosis, and increases G2/M arrest upon cisplatin treatment. Chromatin immunoprecipitation (ChIP), DNA microarray, AR overexpression/knockdown, siRNA GULP1 knockdown, apoptosis assay, cell cycle analysis, cisplatin cytotoxicity assay International journal of molecular sciences Medium 34576193
2023 GULP1 deficiency in male mice increases bone mass due to decreased osteoclast differentiation and function; Gulp1 KO mice show elevated aromatase activity and 17β-estradiol levels in bone marrow, suggesting GULP1 normally suppresses estrogen synthesis and thereby permits osteoclast activity. Gulp1 knockout mice, microcomputed tomography, histomorphometry, in vitro osteoclast differentiation, actin ring and microtubule formation assay, GC-MS for steroid measurement, aromatase activity assay Journal of cellular physiology Medium 36870066
2024 GULP1 interacts with ATG14 (a regulator of autophagosome formation), potentiates class III PI3KC3-C1 activity, and facilitates targeting of ATG14 to the endoplasmic reticulum; a GULP1 mutation disrupting GULP1-ATG14 interaction attenuates this effect; GULP1 increases APP and ATG14 levels in autophagic vacuoles and enhances APP processing by promoting APP entry into autophagic vacuoles. Co-immunoprecipitation, PI3KC3-C1 activity assay, confocal microscopy (ATG14 ER targeting), autophagy flux assay, mutagenesis, APP CTF/Aβ measurement Cellular and molecular life sciences : CMLS High 39080084
2024 Estrogen receptor β (ERβ) directly binds the GULP1 promoter (ChIP assay) and represses GULP1 expression; GULP1 knockdown in bladder cancer increases cisplatin resistance specifically (not resistance to gemcitabine, methotrexate, vinblastine, or doxorubicin). Chromatin immunoprecipitation (ChIP), siRNA knockdown, cisplatin and multi-drug cytotoxicity assay, ERβ overexpression/knockdown Cancer genomics & proteomics Medium 39467629
2024 Gulp1 knockdown impairs chondrocyte growth arrest and differentiation, reduces p21 expression, and attenuates TGF-β/SMAD2/3 pathway activation, demonstrating that Gulp1 contributes to chondrocyte differentiation by modulating TGF-β/SMAD2/3 signaling. siRNA knockdown in ATDC5 cells, chondrogenic differentiation assay, western blot (SMAD2/3 phosphorylation), gene expression analysis FEBS letters Medium 38553249
2024 CED-6/GULP (C. elegans) acts redundantly with clathrin and the AP-2 clathrin adaptor complex to maintain correct CED-1 localization on the plasma membrane, revealing a novel role for CED-6 in CED-1 membrane display beyond its established role in engulfment signaling. C. elegans genetics, genetic epistasis/redundancy analysis with clathrin and AP-2 mutants, CED-1 localization assay G3 (Bethesda, Md.) Medium 38696649
2025 GULP1 deficiency in Gulp1 KO mice reduces tendon cell proliferation (BrdU labeling), diminishes ERK1/2 phosphorylation in tendon cells, downregulates tendon-specific genes (Scleraxis, Mohawk, type I collagen), and disrupts collagen fibrillogenesis (smaller fibril diameters by TEM), resulting in impaired motor coordination. Gulp1 knockout mice, BrdU labeling, western blot (ERK1/2 phosphorylation), qRT-PCR, TEM collagen fibril analysis, gait and motor behavior analysis Acta physiologica (Oxford, England) Medium 40747745
2026 GULP1 directly interacts with IKIP (inhibitor of IKK-interacting protein) to relieve IKIP-mediated suppression of IKKβ-dependent NF-κB activation; this GULP1/IKIP/NF-κB axis upregulates OPA1 expression, restores mitochondrial morphology, and improves fatty acid metabolism in diabetic cardiomyopathy hearts; cardiac-specific GULP1 overexpression attenuates cardiac dysfunction and mitochondrial disruption in diabetic mice. Co-immunoprecipitation (GULP1-IKIP), cardiac-specific knockout and knock-in mice, echocardiography, electron microscopy, enzyme activity assays, ATP and fatty acid oxidation measurements, primary cardiomyocyte experiments Cardiovascular diabetology Medium 42015218

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis. Neuron 229 16772168
2001 Interaction of CED-6/GULP, an adapter protein involved in engulfment of apoptotic cells with CED-1 and CD91/low density lipoprotein receptor-related protein (LRP). The Journal of biological chemistry 204 11729193
1998 Candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C. elegans. Cell 175 9635426
2008 Requirement of adaptor protein GULP during stabilin-2-mediated cell corpse engulfment. The Journal of biological chemistry 90 18230608
1999 Human CED-6 encodes a functional homologue of the Caenorhabditis elegans engulfment protein CED-6. Current biology : CB 60 10574771
1999 The human homologue of Caenorhabditis elegans CED-6 specifically promotes phagocytosis of apoptotic cells. Current biology : CB 57 10574763
2006 The lipoprotein receptor-related protein-1 (LRP) adapter protein GULP mediates trafficking of the LRP ligand prosaposin, leading to sphingolipid and free cholesterol accumulation in late endosomes and impaired efflux. The Journal of biological chemistry 44 16497666
2009 Signalling pathway involving GULP, MAPK and Rac1 for SR-BI-induced phagocytosis of apoptotic cells. Journal of biochemistry 43 19122200
2000 Identification and characterization of a dimerization domain in CED-6, an adapter protein involved in engulfment of apoptotic cells. The Journal of biological chemistry 41 10734103
2020 GULP1 regulates the NRF2-KEAP1 signaling axis in urothelial carcinoma. Science signaling 35 32817372
2010 Adaptor protein GULP is involved in stabilin-1-mediated phagocytosis. Biochemical and biophysical research communications 34 20599701
2007 Regulation of Arf6 and ACAP1 signaling by the PTB-domain-containing adaptor protein GULP. Current biology : CB 28 17398097
2019 Gulp1 controls Eph/ephrin trogocytosis and is important for cell rearrangements during development. The Journal of cell biology 27 31409653
2019 Genomic/proteomic analyses of dexamethasone-treated human trabecular meshwork cells reveal a role for GULP1 and ABR in phagocytosis. Molecular vision 26 31516309
2021 Lnc-GULP1-2:1 affects granulosa cell proliferation by regulating COL3A1 expression and localization. Journal of ovarian research 21 33472700
2021 Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer. International journal of molecular sciences 21 34576193
2018 Integrated transcriptomic and epigenomic analysis of ovarian cancer reveals epigenetically silenced GULP1. Cancer letters 21 29964205
2011 GULP1 is a novel APP-interacting protein that alters APP processing. The Biochemical journal 20 21486224
2014 The adaptor protein GULP promotes Jedi-1-mediated phagocytosis through a clathrin-dependent mechanism. Molecular biology of the cell 19 24743597
2012 The apoptotic engulfment protein Ced-6 participates in clathrin-mediated yolk uptake in Drosophila egg chambers. Molecular biology of the cell 19 22398720
2012 Engulfment protein GULP is regulator of transforming growth factor-β response in ovarian cells. The Journal of biological chemistry 18 22451657
2025 GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma. Clinical and molecular hepatology 13 39914372
2016 Gulp1 is associated with the pharmacokinetics of PEGylated liposomal doxorubicin (PLD) in inbred mouse strains. Nanomedicine : nanotechnology, biology, and medicine 13 27288666
2006 A rat homologue of CED-6 is expressed in neurons and interacts with clathrin. Brain research 13 17007823
2013 Engulfment adaptor phosphotyrosine-binding-domain-containing 1 (GULP1) is a nucleocytoplasmic shuttling protein and is transactivationally active together with low-density lipoprotein receptor-related protein 1 (LRP1). The Biochemical journal 8 23167255
2024 GULP1 as a Downstream Effector of the Estrogen Receptor-β Modulates Cisplatin Sensitivity in Bladder Cancer. Cancer genomics & proteomics 7 39467629
2023 Gulp1 deficiency augments bone mass in male mice by affecting osteoclasts due to elevated 17β-estradiol levels. Journal of cellular physiology 7 36870066
2021 Identification of an Immunogenic Medulloblastoma-Specific Fusion Involving EPC2 and GULP1. Cancers 6 34830991
2012 Cholesterol trapping in Niemann-Pick disease type B fibroblasts can be relieved by expressing the phosphotyrosine binding domain of GULP. Journal of clinical lipidology 6 23415435
2025 Is macropinocytosis more than just a passive gulp? Current opinion in cell biology 5 40220735
2024 GULP1 deficiency reduces adipogenesis and glucose uptake via downregulation of PPAR signaling and disturbing of insulin/ERK signaling in 3T3-L1 cells. Journal of cellular physiology 5 38214103
2024 The cellular adaptor GULP1 interacts with ATG14 to potentiate autophagy and APP processing. Cellular and molecular life sciences : CMLS 5 39080084
2003 Identification of a mouse orthologue of the CED-6 gene of Caenorhabditis elegans. Plasmid 5 12583998
2022 Failure to gulp surface air induces swim bladder adenomas in Japanese medaka (Oryzias latipes). Journal of toxicologic pathology 4 35832900
2017 Expression of GULP1 in bronchial epithelium is associated with the progression of emphysema in chronic obstructive pulmonary disease. Respiratory medicine 4 28284325
2016 A Study to Investigate the Role of GULP/ CED 6 Gene in "Eat Me" Signaling in Cellular Efferocytosis and Immunosurveillance. Immunological disorders & immunotherapy 4 28286882
2024 Gulp1 regulates chondrocyte growth arrest and differentiation via the TGF-β/SMAD2/3 pathway. FEBS letters 3 38553249
2020 Transcription-translation error: In-silico investigation of the structural and functional impact of deleterious single nucleotide polymorphisms in GULP1 gene. Informatics in medicine unlocked 3 33665355
2024 CED-6/GULP and components of the clathrin-mediated endocytosis machinery act redundantly to correctly display CED-1 on the cell membrane in Caenorhabditis elegans. G3 (Bethesda, Md.) 1 38696649
2024 Screening and analysis of GULP1 downstream target genes based on transcriptomic sequencing. Yi chuan = Hereditas 1 39443314
2015 Alcohol detoxification in Ysbyty Gwynedd: Two small sips or one big gulp? Two-step screening more reliable for identification of alcohol dependency syndrome at risk of delirium tremens for routine care. BMJ quality improvement reports 1 26734413
2026 Serum Extracellular Vesicle-Associated GULP1 Is a Key Indicator of Hepatocellular Carcinoma. Oncology research 0 41613803
2026 GULP1 protects against diabetic cardiomyopathy through IKIP/NF-κB-dependent improvement of mitochondrial function. Cardiovascular diabetology 0 42015218
2025 GULP1 Regulates Tendon Cell Proliferation and Maturation Essential for Motor Coordination in Mice. Acta physiologica (Oxford, England) 0 40747745

Missed literature

Know a paper Affinage missed for GULP1? Flag it for the maintainers and the community.

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